The goal of the Human Genome Project is to complete the genome sequence of humans and several model systems. To achieve this goal, order-of- magnitude advances must be made in the development and application of several key technologies. Low cost, high speed DNA sequencing and genotyping is one of these technologies. In the two and one half years of our current program on microfabricated DNA electrophoresis chips, we have succeeded in rapidly developing and routinely operating sequencing devices. Our microchip devices have proved the technology works and we have set the standards for performance of this class of devices. Based on our results and our multidisciplinary expertise, we propose a three year program to build and test 384-lane microfabricated DNA analysis systems under realistic genome center conditions. The systems should provide at least an order of magnitude increase in sequence production with corresponding decreases in overall sequencing costs.